The interactions of bisphosphonates in solution and as coatings on hydroxyapatite with osteoblasts

Aseptic loosening is one of the major causes of failure of artificial hip joints, and it can occur for several reasons, including osteolysis of the bone tissue in response to stress shielding or cellular reactions to wear debris. Any treatment of the prosthesis which could minimize the osteolytic response of bone tissue may be able to extend the life-time of the implant. Bisphosphonates are potent inhibitors of osteoclastic bone resorption, and they bind avidly to hydroxyapatite (HA). Coating the prostheses with bisphosphonates may therefore inhibit osteolysis. We have investigated the potential for this approach by determining whether bisphosphonates interact with osteoblasts in vitro. The effects of pamidronate (P), clodronate (C), and etidronate (E) in solution and when coated onto HA were investigated. P inhibited protein and collagen syntheses potently when in solution, but not after being bound to HA. When bound to HA, both P and C increased DNA, protein and collagen syntheses of osteoblasts and may encourage the osseointegration of implants. The pharmacological effects of the bisphosphonates studied altered dramatically after binding to HA. This must be fully investigated before this approach to prolonging prostheses stability can be evaluated.